Hepatic hemangioendothelioma is a rare and benign vascular tumor, usually asymptomatic at birth. However, it can present with severe cardio-respiratory symptoms and consumptive coagulopathy. Here we present a severe case of hepatic hemangioendothelioma presenting as hydrops fetalis, suggesting that it can have significant prenatal and postnatal morbidity.
This is a unique case of a neonatal hepatic vascular tumor presenting with hydrops fetalis and rapid decompensation after birth. Systemic corticosteroid remains first-line regimen; however, if there is no response, additional therapy such as chemotherapeutic agents and/or surgical interventions is recommended.
A 2545-g male infant was born at 31 weeks’ gestation by an urgent cesarean section to a 26-year-old mother with negative prenatal serology, due to concerns for fetal well-being and meconium-stained fluid. The pregnancy was complicated by maternal anemia, requiring parenteral iron, advanced cervical changes and preterm labor 2 days prior to delivery. Fetal ultrasound showed polyhydramnios, hydrops fetalis, increased fetal abdominal circumference, hepatomegaly with increased vascularity and hyperechogenicity. Resuscitation included endotracheal intubation, positive pressure ventilation and chest compressions for 1 min.
On examination, the infant had generalized edema with moderate respiratory distress. Abdominal examination showed a bluish tinge, distension and hepatomegaly. Global muscle tone was normal with periods of alertness. He was placed on a high-frequency oscillator. Initial arterial blood gas was within normal limits. Complete blood count showed a hematocrit of 32% and a platelet count of 45,000/mm3.
Abdominal ultrasound revealed a large, heterogeneous, hypoechoic hepatic mass (Figure 1) with multiple areas of arterio-venous shunting and dilated tortuous hepatic veins, consistent with the diagnosis of hepatic hemangioendothelioma. A chest radiograph showed prominent hepatic density consistent with ultrasound findings and prominent cardiac silhouette concerning for pulmonary overcirculation.
An echocardiogram showed dilated atria and ventricles with a mildly depressed right ventricular function. The alpha fetoprotein (AFP) level was 125,000 ng/mL (normal for age 134,734 ± 41,444). Phototherapy was started for hyperbilirubinemia within 24 h of life. The infant developed consumptive coagulopathy, anemia and thrombocytopenia, for which he was given multiple transfusions. He was started on methylprednisolone (1 mg/kg/dose every 6 h), propranolol (0.33 mg/kg/dose every 8 h) and received a dose of vincristine (0.05 mg/kg) but showed no improvement. Eventually, embolization of the left hepatic artery and branch of the left inferior phrenic artery was performed using multiple microcoils and microvascular plugs (Figure 2). Anemia and thrombocytopenia stabilized within 48 h, at which point methylprednisolone and propranolol were discontinued. Complete resolution without further transfusions was achieved. A post-treatment echocardiogram showed improved function of right ventricle. The hepatic mass was followed by serial ultrasounds and demonstrated continuous decrease in size.
Hepatic vascular tumors presenting as hydrops fetalis have rarely been reported. An ideal therapeutic approach has also not been described. This is a rare case presenting with severe symptoms immediately after birth and successfully cured by hepatic artery embolization.
Etiologies for non-immune hydrops fetalis can be classified into the following major categories :
Cardiovascular disease (20%)
Lymphatic dysplasia (15%)
Syndromic causes without a known genetic defect
Twin-to-twin transfusions and placental vascular abnormalities
A fetal ultrasound of this neonate had already suggested the possibility of hepatic mass causing hydrops.
The differential diagnosis for a neonate presenting with congenital hepatic mass should include the three most common tumors: hemangioma/hemangioendothelioma (60%), mesenchymal hamartoma (23%) and hepatoblastoma (16%) .
Hepatic hemangioendothelioma is a rare benign vascular tumor arising from mesenchymal tissue. There are two types of hemangioendothelioma. Type 1 is made up of variably sized vascular spaces lined with a layer of endothelial cells in fibrous stoma and contain biliary ducts. Type 2 has larger pleomorphic endothelial cells without biliary ducts .
Infantile hemangioendotheliomas are commonly asymptomatic at birth. However, they can lead to arterio-venous shunting with congestive cardiac failure, tachypnea and failure to thrive. Congestive cardiac failure, as reported, leads to increased central venous pressure and is the probable cause of hydrops formation. This can also lead to difficult cardiac pre-load, causing severe symptoms like abdominal distension, hepatomegaly, intraabdominal hemorrhage and poor feeding. There may be anemia, thrombocytopenia and consumptive coagulopathy, also known as Kasabach-Merritt syndrome. Elevated AFP may or may not be present. Thyroid dysfunction may be seen due to production of a thyroid-stimulating hormone (TSH)-like protein from the endothelial cells or increased destruction of normal thyroid hormones by type 3 iodo-thyronine deiodinase.
Initial evaluation should include ultrasound with Doppler. This may show iso- or hypoechoic areas with increased vascularity. A contrast-enhanced computed tomography (CECT) scan may show a hypodense area with contrast enhancement. Angiography delineates the vascular supply. Biopsies are usually unnecessary and should be avoided due to risk of uncontrollable hemorrhage.
In severe antenatal cases, intrauterine transfusions of packed red blood cells (RBCs) and platelets are administered to support the fetus, although it is controversial if repeat transfusions are beneficial. The use of maternal corticosteroids in severe cases of high-output fetal cardiac failure has also been documented , .
After birth, asymptomatic lesions can be followed using serial ultrasound. A systemic corticosteroid is usually the first-line regimen, which inhibits proliferation of endothelial cells. Treatment using α-interferons may be an option to inhibit endothelial cell proliferation, migration and angiogenesis. However, potential adverse effects including bone marrow depression and elevated liver enzymes have led to its decreased use. Chemotherapeutic agents such as vincristine and β-blockers such as propranolol have been used to show tumor regression .
Embolization of feeding vessels can be performed by interventional radiologists. Unilobar tumors may be surgically resected. Finally, for symptomatic lesions not suitable for embolization or resection, liver transplantation should be considered.
Conflict of interest: Authors disclose no conflict of interest.
Material and Methods
Informed consent: Informed consent has been obtained from all individuals included in this study.
Ethical approval: The research related to human subject use has complied with all the relevant national regulations, and institutional policies, and is in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.
Funding: Dr. Cheung wrote the first draft of the manuscript and no honorarium was paid to anyone to produce this manuscript.
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